- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Batta, I., Ajith, M., Calhoun, V.In studying the brain's functional connectivity and its associations with clinically observed assessments, novel learning frameworks modeling its network properties in conjunction with assessment variables are crucial to uncover variable-specific patterns via meaningful encoding and reconstruction. We present a generative framework for modeling human brain functional connectivity features while retaining key network metrics and differences associated with demographic and cognitive variables. A conditional graph variational autoencoder is employed to encode static functional network connectivity (sFNC) features into a latent representation, […]
- by Min, J., Vishnyakova, O., Brooks-Wilson, A., Elliott, L. T.Identifying physiological sweet spots (optimal ranges for homeostasis) is essential for precision medicine. However, traditional statistical methods often rely on globally linear or locally jagged models that struggle to capture the smooth, non-linear nature of biological regulation in high-dimensional data. We present the Quantile Feature Selection Network (Q-FSNet), a neural network-based framework that integrates quantile regression, feature selection, and uncertainty estimation to identify biomarkers with sweet spots. Unlike traditional methods, Q-FSNet learns continuous response curves without requiring pre-specified number of […]
- by Yang, T., Walker-Hale, N., Yang, F., Zeng, C., He, Z.-S., Chomicki, G., Xu, W., Chen, G.Seed dispersal by wasps (vespicochory) is documented in five angiosperm families, with phylogenies suggesting that most vespicochorous lineages evolved from ant-dispersed (myrmecochorous) ancestors. While recent work has identified cues attracting wasp dispersers, the molecular basis remains unclear. To shed light on the molecular basis of vespicochory, we generated chromosome-level genomes for the wasp-dispersed Stemona tuberosa, and its close ant-dispersed relative S. mairei. Combining comparative genomic, transcriptomic, lipidomic, and functional analyses, we ask (i) how chemical elaiosome differentiation occurs during seed […]
- by Orellana, E. A., Bowles, I. E., Yang, X., Torres, A., Jamieson, S. R., Ali, R. H., Gutierrez, A., Gregory, R. I.tRNAs play a critical role in protein synthesis, influencing mRNA translation dynamics to shape proteomes. Emerging evidence links dysregulated tRNA activity to cancer progression, with tRNA-Arg-TCT identified as an oncogenic driver when ectopically overexpressed in non-malignant cells. The requirement of endogenous tRNA-Arg-TCT in cancer biology, however, remains untested. Moreover, considering that the tRNA-Arg-TCT family comprises six genes in humans, the importance of an individual tRNA isodecoder in cancer remains unknown. Here, we find elevated levels of tRNA-Arg-TCT-4-1 isodecoder are associated […]
- by Ma, Z., Liu, M., Wang, S., Wang, S., Zang, C.Spatial organization of the genome plays a vital role in defining cell identity and regulating gene expression. The three-dimensional (3D) genome structure can be measured by sequencing-based techniques such as Hi-C usually on the cell population level or by imaging-based techniques such as chromatin tracing at the single-cell level. Chromatin tracing is a multiplexed DNA fluorescence in situ hybridization (FISH)-based method that can directly map the 3D positions of genomic loci along individual chromosomes at single-molecule resolution. However, few computational […]
- by Pedigo, B. D., Danskin, B. P., Swanstrom, R., Neace, E., Dorkenwald, S., da Costa, N. M., Schneider-Mizell, C. M., Collman, F.Neurons display a remarkable sub-cellular specificity in their synaptic targeting, which varies by cell type–for example, excitatory neurons prefer to target the spines of other excitatory cells. Modern dense neuroanatomy data, such as large volumetric electron microscopy connectomes, enable the study of this sub-cellular specificity and its context in a circuit at unprecedented scale and resolution. However, this scale has also made it challenging to create accurate and efficient methods for classifying and segmenting fine cell components (including spines) across […]
- by Hayashi, S., Takeuchi, M., Nakano, T., Setoyama, D., Singh, S. A., Sonawane, A. R., Iwamoto, T., Kishimoto, H., Tsuchimoto, A., Yamada, S., Kang, D., Ago, T., Kitazono, T., Aikawa, M., Kunisaki, Y.Focal segmental glomerulosclerosis (FSGS) is a major cause of glucocorticoid-resistant nephrosis, yet its pathogenesis remains unclear. To define the molecular and cellular landscape of FSGS, we employed multi-omics approaches on independent human kidney biopsy cohorts. Proteomics revealed enhanced immune and complement activation. Spatial transcriptomics using a target gene panel constructed from the proteomics highlighted alternative pathway activation driven by complement factor D as a prominent feature. Complement activation emerged in glomeruli alongside altered signaling in podocytes and parietal epithelial cells […]
- by Majeed, M., Akram, M. Z., Tariq, H.Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks effective targeted therapies. This study aimed to identify robust prognostic biomarkers by integrating network biology with machine learning (ML) approaches. TNBC expression cohorts were analysed to identify differentially expressed genes (DEGs) and crucial gene clusters via limma and Weighted Gene Co-expression Network Analysis (WGCNA). In results, 579 DEGs were identified, and network analysis revealed two TNBC-associated modules. Overlapping determined 208 genes enriched in cell-cycle and mitotic-regulation pathways. To identify candidate […]
- by Hong, L., Liu, M., Sridhar, S., Ong, Z. Y. C., Tay, S. C. N., Lai, W. X. C., Tipgomut, C., Jaynes, P., Peng, Y., Tan, C. L., Hue, S. S.-S., Ng, S.-B., Mel, S. D., Poon, L., Batumalai, Y., Jayalakshmi,, Brooks, J., Hamberger, F., Lane, B. J., Jimenez-Sanchez, D., Braubach, O., Pan-Hammarstrom, Q., Sudharshan, R., Tsang, A., Rao, A., Keller, E. T., Hawula, Z., Burgess, M., Tuczko, N., Keane, C., Ponzoni, M., Tripodo, C., Jeyasekharan, A. D.Primary central nervous system lymphoma (PCNSL) is a subtype of diffuse large B-cell lymphoma (DLBCL) with confined CNS growth. We evaluated tumor microenvironment (TME) features associated with its unique tropism. Comparative spatial transcriptomic profiling of PCNSL samples (n=17) revealed increased macrophage infiltration compared to systemic DLBCL (n=76). These macrophages showed enrichment of immunosuppressive (SPP1) and cholesterol metabolism signatures. These findings were validated across three independent PCNSL scRNA-seq cohorts (n=8,7,13), with further characterization as lipid-laden macrophages (LLMs)- like those noted in […]
- by Roshchina, M., Yin, H.The parafascicular nucleus (Pf), part of the intralaminar thalamic nuclei, has been implicated in diverse functions such as attention, nociception, and behavioral flexibility, yet its precise contributions to behavior remain poorly defined. In this study, we used optogenetics in male and female mice to study the role of Pf projection neurons using high-resolution and continuous measures to quantify both skeletomotor and autonomic behavioral outputs as well as motivational valence. We showed that selective Pf stimulation resulted in wide-ranging effects, including […]
- by Matsumoto, H., Kang, Z., Nonoyama, T., Kimata, Y., Tsugawa, S., Ueda, M.The zygote is the origin of development, and in most angiosperms, it divides asymmetrically to establish the apical-basal axis. In Arabidopsis thaliana, the zygote undergoes tip growth-like polar elongation, using a subapical transverse microtubule band (MT band). Because canonical tip-growing cells rely on longitudinal actin filaments (F-actin), it remains unclear whether and how the zygote employs conserved tip-growth mechanisms. Here, using quantitative live-cell imaging, pharmacological perturbations, and mechanical simulations, we found that oscillatory Ca2+ waves, a hallmark of tip growth, […]
- by Rhoades, K. E. B., Goeckeritz, C. Z., Bird, K. A., Yocca, A. E., Edger, P. P., Iezzoni, A.Subgenome dominance is a phenomenon observed in many allopolyploids where one parental genome exhibits stronger influence over phenotype than the other parental genomes. This may present as preferential retention of one subgenome through fractionation, replacement via homoeologous exchange, or as subgenome expression bias, where one subgenome is expressed at a higher abundance compared to other subgenomes. Sour cherry (Prunus cerasus) is an allotetraploid fruit tree species resulting from an interspecific cross between extant relatives of ground cherry (P. fruticosa) and […]
- by Li, C. Y., Grob, A., Repa, L., Huxley, O., Brotherton, D. H., Becker, P., Dadzie, R., Beckstein, O., Cameron, A. D.ASBT and NTCP are sodium-coupled secondary transporters of the SLC10 family that play critical roles in the enterohepatic recycling of bile acids. Secondary transporters generally function through the alternating access mechanism. However, in outward-facing structures of NTCP this mechanism is violated with a pore running through the protein. No such pore is observed in previously reported structures of bacterial ASBT homologues, but these proteins have an additional transmembrane-helix adjacent to the binding site. Here we investigate another homologue of ASBT […]
- by Feng, Z., Chen, F., Xiao, J., Du, A., Deng, J., Zhang, Y., Li, X., Zheng, A., Li, H.Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition that progresses from simple steatosis to advanced fibrosis, significantly affecting liver function and systemic health. Despite its widespread impact, therapeutic options are limited, highlighting the urgent need for comprehensive exploration to identify potential therapeutic targets. In this study, we created an analysis pipeline anchored on liver gene expression, integrating differential meta-analysis of transcriptomic data across three MASLD stages, transcriptome-wide Mendelian randomization (MR), and transcriptome-wide association studies (TWAS), to identify 39 […]
- by Chen, P., Cui, Z., Constantinidis, C.Understanding function from structure is a central topic in both neurobiology and artificial intelligence. In the human brain, macroscale functional organization, including functional parcellations, modules, and hierarchies, has been systematically linked to anatomical structure, providing an interpretable and clinically meaningful framework for linking structure to function. In contrast, although artificial neural networks are widely used as models of cognition, prior studies have not incorporated comprehensive macroscale brain structural constraints into model design, and artificial neural networks are rarely interpreted in […]
- by Kuznetsov, A. V.AA amyloidosis is a severe complication of chronic inflammatory diseases characterized by fibrillar protein deposition in the kidneys, leading to progressive organ failure. This study presents a mathematical model coupling SAA-HDL binding dynamics with renal amyloid aggregation kinetics to elucidate disease pathogenesis. Under normal conditions, Serum Amyloid A (SAA) circulates bound to high-density lipoprotein (HDL), which acts as a molecular chaperone preventing misfolding. However, during chronic inflammation, SAA production exceeds HDL binding capacity, resulting in free SAA that undergoes renal […]
- by Zhang, J., Hong, F., Kim, J., Bakhurin, K., Kim, N., Yin, H.Calcium imaging with miniature endoscopes has become an essential tool in neuroscience, but conventional miniscopes typically record signals from only a single calcium indicator. Here, we present a dual-color miniature endoscope (miniscope) that enables simultaneous calcium imaging from two neuronal populations using spectrally distinct genetically encoded indicators. In freely moving mice, we used this system to record activity from striatal neurons of the direct (dSPN) and indirect (iSPN) pathways. We showed that dSPNs were activated earlier than iSPNs during contraversive […]
- by Xia, T., Zhao, X., Islam, S. S. M., Mohammed, K. K., Xie, Z., Zhi, D.Magnetic resonance imaging (MRI)-derived phenotypes (IDP) has enabled the discovery of numerous genomic loci associated with brain structure and function. However, most existing IDPs and learned representations are derived from a single imaging modality, missing complementary information across modalities and potentially limiting the scope of genetic discovery. Here, we introduce a multimodal contrastive learning framework to derive heritable representations from paired T1- and T2-weighted MRIs. Unlike single-modality reconstruction-based models, we designed a momentum-based contrastive learning framework. As a result, our […]
- by Collins, K., Stanley, C. E., Ouldridge, T. E.Microfluidic devices with surface-bound biomolecular patterns enable localised detection arrays, enzymatic catalysis, and gene expression. Photolithography is a contactless patterning method with high spatial control. However, while patterning open surfaces by photolithography is well-established, patterning enclosed microfluidic channels remains technically challenging. Such capability would enable in situ surface modification and precise pattern alignment to channel geometries. Here, we present a photolithographic method using commercially available reagents to pattern sealed microfluidic devices. We first coat surfaces with (3-Aminopropyl)triethoxysilane (APTES) to bond […]
- by Liu, J., Wang, B., Catrow, J. L., Pearce, Q., Ji, Z., Yang, S. W., Balakrishnan, A., Cox, J., Ma, D. K.Suspended animation, a state of extreme quiescence with microscopically invisible movement and development, is a remarkable yet poorly understood stress resilience strategy in animals. Here, we describe a newly discovered form of suspended animation inducible by high-population density in isosmotic liquids in C. elegans throughout larval development and adulthood. Transcriptomic, metabolomic and live-cell activity reporter imaging analyses reveal striking molecular and cellular landscape changes by such liquid-induced suspended animation (LISA), including remodeling of gene expression programs, energy metabolites, lysosomal and […]